1. Field of Invention
The present invention relates to a composition for preventing, improving, or treating Th1-mediated immune diseases or Th2-mediated immune diseases comprising one or more extracts as active ingredients selected from kaladana (Pharbitis nil Choisy), cassia seeds (Senna obtusifolia L.), spurge (Euphorbia pekinensis), spikenard (Nardostachys jatamanse), wrinkled giant hyssop (Agastache rugosa), roots of Phytolaccaceae (Phytolacca esculenta), inner skin of Castanea crenata (Castanea crenata S.), white pharbitis seeds (Pharbitis nil Chois), fruits of Rosa multiflora (Rosa multiflora) and rhubarbs (Rheum rhabarbarum L.); and a method for preventing, improving, or treating histamine-mediated diseases
2. Background Art
In recent years, allergies have increased due to various reason including changing dietary habits, better hygiene and intensified pollution along with advancement in income levels, and about 20-25% of the entire population have symptoms of, for example, atopic dermatitis (AD), asthma and rhinitis. These significantly affect the quality of life, and may lead to serious social issues. Also, it cannot be ignored that food allergies are found in 6-8% of infants and also cause 35% of children's ADs.
Until now, a medicine that shows definite effects against various allergies has not existed and, thus, treating children who have these allergies has been especially difficult even though children's ADs have been on the rise. Particularly, drugs that have similar characteristics as steroids bring about serious side effects so there are currently attempts around the world to prepare for alternative solutions. To combat these allergies, materials that are expected to have positive results without any toxicity or side effects must be extracted from natural substances and foods, which then should be actively utilized. Moreover, the anti-allergy mechanism of action for active materials and their components must be also examined in detail.
The main-stream medicine popular in the 21st century have been those for allergies and diabetes (Japan's Nikkei Sankyo Newspapers). In the United States, around 50 million people possess many different kinds of allergies (drug and medicine market, $5.2 billion annually). In Japan, there exists a market for functional foods worth around 60 billion JPY while that of drugs and medicine related to allergies is worth 156 billion JPY annually, compared to the Korean market for drugs and medicine, which is worth around 50 billion KRW. Looking at the recent trend of patents in functional foods, most of the ones submitted are in the area of “anti-obesity”, followed by “anti-allergy”, an area that is anticipated to be of much added value but also requires necessary preparation.
There has been an increasing need for development of health functional foods, emphasizing immune function controls or activation of allergy suppression, which has resulted in numerous patents submitted to the Korea Food and Drug Administration. Also, according to patent analyses in Japan during recent years, the future potential for functional foods was reported to lie in the activation of “anti-obesity” and then “anti-allergy”.
The term “allergy” has been originated from a Greek word “allos”, which means “hypersensitive reaction”, and refers to the “deformed”. In other words, an allergy is an occurrence caused by a substance, which has no effect on average people, inducing abnormally hypersensitive reaction such as hives, itching, nasal discharges and/or coughs on a particular individual due to malfunctioning of the immune system. In the last 20 years, the incidence rate of allergic diseases has been trending upward globally (1, 2). Primary reasons for this increase include more time spent indoors, development of new materials, sudden influx of allergy-inducing materials particularly from overseas, unstable immune statuses due to environmental contamination and stress, and changing dietary habits. Although the incidence rate of allergic diseases in the people of modern era has steadily increased, many only rely on well-known treatments such as anti-histamines or steroids without finding a fundamental treat for it (3).
Gell and Coombes (1963) traditionally divide allergic reactions into 4 categories based on time and types of manifestation (4). Types I through III are humoral immunologic responses (immediate-type) in which antibodies are involved while Type IV is a cellular immunologic response (delayed-type). Also, based on the types of cells and medium concerned with immune reactions, responses are divided into immediate or early responses in which symptoms are displayed within minutes, and late-stage responses in which symptoms appear after a few hours. For example, Type I takes the form of an immediate hypersensitive reaction while Type IV is a delayed hypersensitive reaction. Most allergic reactions are categorized as Type I, which includes diseases such as asthma, rhinitis, conjunctivitis, food and drug allergies and atopic dermatitis, and severe cases lead to anaphylaxis, which may risk one's life.
Type I immediate hypersensitive reactions are further divided into 2 steps. In the first step, allergen penetrates into a body and suppresses secretion of IgE and IgG1. Once the balance between Th1 cellular response, which produces IL-12 and IFN-r that increase secretion of IgG2a, and Th2 cellular response, which produces IL-4, IL-5 and IL-13, tips in the direction of Th2, IL-4, IL-13 and others are discharged due to an excessive hypersensitive reaction of Th2. Because of this effect, IgE specific antibodies produced by B cells are attached to mast cells or basophils, and, subsequently, an allergic crisis is ready, all of which is called the sensitization of allergens (5-7) (Refer to figure: “Allergic Diseases”, “Th1/Th2 Balance”).
The second step of allergic crisis is divided into early and late responses. In the early response, an allergen re-penetrates the body, stimulates mast cells and induces degranulative reactions, releasing histamines, lipid metabolites and Cytokine at this time to cause blood vessels to expand. In the late response, neutrophils, eosinophils, macrophage, Th2 cells and basophils infiltrate into a particular tissue and are activated, which leads to inflammation and symptoms of atopic dermatitis, rhinitis and asthma (7). Among these secreted matters of degranulation, histamine is the most well-known and used as an essential indicator for allergic symptoms due to its relations to immediate hypersensitive reactions (8).
On the other hand, food allergies have occurred in about 3 to 6% of children in developed countries for the past 10 years and show an upward trend (9). Food allergies, which are caused by food coming into a body through the digestive tract, belong primarily to Type I hypersensitive reaction. For allergy patients, food allergens penetrate through intestinal canals at an undigested state (4, 10) and, thus, the absorption of allergens inside intestines is the first step of an allergic crisis (11). Intestinal canals not only take care of digestion and absorption of nutrients but also are involved in various biomodulation. Primary characteristics of intestinal epithelial cells include digestion and absorption, the role as a barrier and transfer and conversion of food signals. As they also possess developed a special immune system (mucosal immunity) and nerve tissues, the role of digestive and intestinal canals must not be underestimated. Thus, as a barrier, intestinal epithelial cells restrict the penetration of large molecules by a tight junction; however, if the tight junction is damaged, the permeability increases due to the dysfunction of the barrier, which may result in diseases such as food allergies, celiac disease and acute pancreatitis (12-17). In other words, food allergies can be prevented by strengthening the barrier function of intestinal canals through stabilization of tight junction.
The research papers previously mentioned have reported, to a great extent, about the activation of the allergy inhibition in foods and natural products, which have been popularly used especially by Koreans in oriental medicine and home remedies to treat and prevent allergies (18, 19). These research mostly evaluate the activation of degranulation inhibition in medicinal herbs such as areca nuts, Anemarrhena rhizome and fenugreek (20-33) and also report on Th1/Th2 immune response controls in polysaccharide components such as quercetin, Siberian gooseberries, garlic, perilla oil, konjac, lobulus and liriope rhizome in addition to those in Lingzhi mushrooms and Japanese soy sauce as well as royal jelly and cordyceps (34-44). Also reported were results on the activation which suppresses allergic inflammation in lactobacillus, fermented barley and cheonggukjang, a Korean fermented soybean soup (45-49).
Throughout the entire specification, many papers and patent documents are referenced and their citations are represented. The disclosures of cited papers and patent documents are entirely incorporated by reference into the present specification, and the level of the technical field within which the present invention falls and details of the present invention are explained more clearly.